ArticleExperimental hematology & oncology2024
Multi-model analysis of gallbladder cancer reveals the role of OxLDL-absorbing neutrophils in promoting liver invasion.
Article in Experimental hematology & oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- OLR1 drives gastric cancer progression through NF-κB activation and immunosuppressive macrophage polarization.Medical oncology (Northwood, London, England) · 2026Article
- Neutrophil-based immunotherapy: A metabolic lens on mechanisms and therapeutic implications.Clinical and translational medicine · 2026Review
- Targeting CD74 may mitigate immune-escape features and enhance BCMA CAR-T activity in preclinical models of relapsed/refractory multiple myeloma.Journal for immunotherapy of cancer · 2026Article
- Spatial profiling defines three immunophenotypes and a perineural invasion-associated immune-evasion niche in gallbladder cancer.JHEP reports : innovation in hepatology · 2026Article
- Mapping of Neutrophils in Cancers: Insights From Spatial Omics Technologies.European journal of immunology · 2026Review
- Targeting FN1 to overcome gemcitabine resistance in gallbladder cancer: Mechanistic insights and an iRGD-modified PEG-PLGA nanoparticle delivery strategy.Materials today. Bio · 2026Article
- Macrophage-rich niches regulate T cell dynamics at the liver invasive margin during gallbladder cancer progression.The Journal of clinical investigation · 2026Article
- Spatiotemporal dynamics of tumor-associated neutrophils: bridging the gap between cancer progression and immunotherapy.Molecular cancer · 2026Review
- Correction: Multi-model analysis of gallbladder cancer reveals the role of OxLDL-absorbing neutrophils in promoting liver invasion.Experimental hematology & oncology · 2025Article
- Integrating Machine Learning and Multi-Omics to Explore Neutrophil Heterogeneity.Biomedicines · 2025Review
- Spatial immune remodeling of the liver metastases: discovering the path to antimetastatic therapy.Journal for immunotherapy of cancer · 2025Review
- Review
- Prognostic value of the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) in patients with RAS-mutant metastatic colorectal cancer.Frontiers in nutrition · 2025Article
- M2-like tumor-associated macrophage-secreted CCL2 facilitates gallbladder cancer stemness and metastasis.Experimental hematology & oncology · 2024Article
- Focusing on the Immune Cells: Recent Advances in Immunotherapy for Biliary Tract Cancer.Cancer management and research · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
19 authors.
Funding
Abstract
backgroundGallbladder cancer (GBC) is the most common and lethal malignancy of the biliary tract that lacks effective therapy. In many GBC cases, infiltration into adjacent organs or distant metastasis happened long before the diagnosis, especially the direct liver invasion, which is the most common and unfavorable way of spreading.
methodsSingle-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), proteomics, and multiplexed immunohistochemistry (mIHC) were performed on GBC across multiple tumor stages to characterize the tumor microenvironment (TME), focusing specifically on the preferential enrichment of neutrophils in GBC liver invasion (GBC-LI).
resultsMulti-model Analysis reveals the immunosuppressive TME of GBC-LI that was characterized by the enrichment of neutrophils at the invasive front. We identified the context-dependent transcriptional states of neutrophils, with the Tumor-Modifying state being associated with oxidized low-density lipoprotein (oxLDL) metabolism. In vitro assays showed that the direct cell-cell contact between GBC cells and neutrophils led to the drastic increase in oxLDL uptake of neutrophils, which was primarily mediated by the elevated OLR1 on neutrophils. The oxLDL-absorbing neutrophils displayed a higher potential to promote tumor invasion while demonstrating lower cancer cytotoxicity. Finally, we identified a neutrophil-promoting niche at the invasive front of GBC-LI that constituted of KRT17
conclusionsOur study reveals the existence of a subset of pro-tumoral neutrophils with a unique ability to absorb oxLDL via OLR1, a phenomenon induced through cell-cell contact with KRT17
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